Mesenchymal Stem Cells Repress Osteoblast Differentiation Under Osteogenic‐Inducing Conditions

Abstract

This study was designed to investigate the influence of mesenchymal stem cells (MSCs) on osteoblast (OB) differentiation. Rat bone marrow MSCs were cultured either in growth medium that maintained a MSC phenotype or in osteogenic medium that induced differentiation into OBs. Then, cells were grown in two different culture conditions: indirect co-culture of MSCs and OBs and OBs cultured in MSC-conditioned medium. As a control culture condition, OBs were grown in osteogenic medium without the influence of MSCs. We evaluated cell proliferation, the gene expression of key bone markers, alkaline phosphatase (ALP) activity, bone sialoprotein (BSP) expression, and extracellular matrix mineralization. The results showed that, regardless of whether OBs were indirectly co-cultured with MSCs or cultured in MSC-conditioned medium, MSCs repressed OB differentiation, as evidenced by the downregulation of all evaluated bone marker genes, decreased ALP activity, inhibition of BSP protein expression, and reduced extracellular matrix mineralization. Taken together, these results indicate that despite the key role of both MSCs and OBs in the osteogenic process, the repressive effect of MSCs on OB differentiation in an osteogenic environment may represent a barrier to the strategy of using them together in cell-based therapies to induce bone repair.

Co-Culture with Human Osteoblasts and Exposure to Extremely Low Frequency Pulsed Electromagnetic Fields Improve Osteogenic Differentiation of Human Adipose-Derived Mesenchymal Stem Cells

“…In the work of Birmingham and colleagues, however, only co-cultures with osteocytes improved AP activity and matrix mineralization of MSCs [ 16 ]. Santos and colleagues even showed inhibitory effects of B-MSCs on osteogenic differentiation of osteoblasts [ 29 ]. This is contrary to our findings, where the co-cultures favored AP activity and matrix mineralization, as compared to the individual mono-cultures.…”

“…The observed discrepancies with some of the reported studies might be explained by differences in the osteogenic differentiation potential of MSCs isolated from different sources. Ad-MSCs might have a better osteogenic potential than B-MSCs when exposed to certain factors, such as PDGF-BB [ 29 ]. Our results presented here indicate that Ad-MSCs also improve their osteogenic potential when co-cultured with osteoblastic cells.…”

Emerging Role of Extracellular Vesicles in Bone Remodeling

“…BMSCs play a vital role in osteoblastic differentiation via the paracrine pathway (Santos et al 2015). Recent studies have demonstrated that when cocultured with human osteoblasts (hFOB 1.19), PKH67-labeled BMSC-EVs are distributed in organelles, such as the endoplasmic reticulum, Golgi apparatus, and lysosomes of these osteoblasts.…”

A protocol for isolation and identification and comparative characterization of primary osteoblasts from mouse and rat calvaria

“…Osteoblast differentiation was regulated by some factors which were released during bone resorption to ensure the new bone formation (Cao 2011 ). MSCs repress osteoblast differentiation under osteogenic-inducing conditions (Santos et al 2015 ). Thus, it makes sense to make clear the relationship between osteoblast with other cells and through what factors they function in bone formation.…”